Open AccessJournal Article
Loss of Heterozygosity Involves Multiple Tumor Suppressor Genes in Human Esophageal Cancers
Ying Huang,Robert F. Boynton,Patricia L. Blount,Richard J. Silverstein,Jing Yin,Yi Tong,Timothy K. McDaniel,Carnell Newkirk,James H. Resau,Rajeshwari Sridhara,Brian J. Reid,Stephen J. Meltzer +11 more
TLDR
The data suggest that allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletion involving MCC may not occur independently of deletions involving other tumor suppressing genes; and (c) the accumulation of multiple allelic deleting involving specific tumor suppresser genes may be important in most esphageal tumorigenesis or tumor evolution.Abstract:
Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.read more
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Journal Article
Diagnostic Microsatellite Instability: Definition and Correlation with Mismatch Repair Protein Expression
TL;DR: These studies provide a clear recommendation for the uniform use of a panel of 10 microsatellites and a definition of at least 40% instability (using these defined marker loci) in the diagnostic analysis of MSI.
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Barrett's esophagus, dysplasia, and adenocarcinoma
TL;DR: Dysplasia precedes adenocarcinoma in Barrett's esophagus and arises from the metaplastic epithelium; it has been proposed as a marker for detecting patients at high risk for developing carcinoma.
Journal ArticleDOI
Hypermethylated APC DNA in Plasma and Prognosis of Patients With Esophageal Adenocarcinoma
Kazuyuki Kawakami,Jan Brabender,Reginald V. Lord,Susan Groshen,Bruce D. Greenwald,Mark J. Krasna,Jing Yin,A. Steven Fleisher,John M. Abraham,David G. Beer,David Sidransky,Harold T. Huss,Tom R. DeMeester,Cindy A. Eads,Peter W. Laird,David H. Ilson,David P. Kelsen,David H. Harpole,Mary Beth H. Moore,Kathleen D. Danenberg,Peter V. Danenberg,Stephen J. Meltzer,Stephen J. Meltzer +22 more
TL;DR: Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.
Journal ArticleDOI
Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.
Janusz Jankowski,Nicholas A. Wright,Stephen J. Meltzer,George Triadafilopoulos,K. Geboes,Alan G. Casson,David J. Kerr,Lawrence S. Young +7 more
TL;DR: This work focuses on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally.
Journal Article
Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma.
Cindy A. Eads,Reginald V. Lord,Soudamini K. Kurumboor,Kumari Wickramasinghe,Margaret L. Skinner,Tiffany I. Long,Jeffrey H. Peters,Tom R. DeMeester,Kathleen D. Danenberg,Peter V. Danenberg,Peter W. Laird,Kristin A. Skinner +11 more
TL;DR: The spatial distribution of methylation patterns in six esophagectomy cases in detail is mapped and it is shown that normal esophageal squamous epithelium is unmethylated at all four CpG islands, and CDH1 is unm methylated in most other tissue types as well.
References
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Book
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Journal Article
Construction of a genetic linkage map in man using restriction fragment length polymorphisms.
TL;DR: A new basis for the construction of a genetic linkage map of the human genome is described, to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA.
Journal ArticleDOI
Genetic alterations during colorectal-tumor development.
Bert Vogelstein,Eric R. Fearon,Stanley R. Hamilton,Scott E. Kern,Ann C. Preisinger,Mark Leppert,A M Smits,Johannes L. Bos +7 more
TL;DR: It is found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas, which are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumors.
Journal ArticleDOI
Hypervariable 'minisatellite' regions in human DNA.
TL;DR: A probe based on a tandem-repeat of the core sequence can detect many highly variable loci simultaneously and can provide an individual-specific DNA ‘fingerprint’ of general use in human genetic analysis.
Journal ArticleDOI
Identification of FAP locus genes from chromosome 5q21
Kenneth W. Kinzler,Mef Nilbert,Li Kuo Su,Bert Vogelstein,Tracy M. Bryan,Daniel B. Levy,Kelly J. Smith,Antonette C. Preisinger,Hedge Philip John,Douglas McKechnie,Rachel Finniear,Alex Markham,John Groffen,Mark S. Boguski,Stephen F. Altschul,Akira Horii,Hiroshi Ando,Yasuo Miyoshi,Yoshio Miki,Isamu Nishisho,Yusuke Nakamura +20 more
TL;DR: The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein, and these two closely spaced genes encode proteins predicted to contain coiled-coil regions, which were also expressed in a wide variety of tissues.